scholarly journals The Effect of 4′-hydroxy-3,4,5-trimetoxystilbene, the Metabolite of Resveratrol Analogue DMU-212, on Growth, Cell Cycle and Apoptosis in DLD-1 and LOVO Colon Cancer Cell Lines

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1327
Author(s):  
Malgorzata Jozkowiak ◽  
Paulina Skupin-Mrugalska ◽  
Andrzej Nowicki ◽  
Sylwia Borys-Wojcik ◽  
Marcin Wierzchowski ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Lovo Cell ◽  
Cycle Arrest ◽  
Colon Cancer Cell Lines ◽  
M Phase ◽  
Extrinsic Apoptosis

Resveratrol is a phytoalexin that naturally occurs in grapes, blueberries, cranberries, peanuts and many other plants. Although resveratrol inhibits carcinogenesis in all three stages, its clinical application is restricted due to poor pharmacokinetics. The methylated analogues of resveratrol have been found to have higher bioavailability and cytotoxic activity than that of the prototupe compound. Among the various methoxy derivatives of resveratrol, 3,4,5,4′-tetrametoxystilbene (DMU-212) is suggested to be one of the strongest activators of cytotoxicity and apoptosis. DMU-212 has been shown to exert anti-tumor activity in DLD-1 and LOVO colon cancer cells. Since colorectal cancer is the third most common cause of cancer-related deaths worldwide, the development of new anticancer agents is nowadays of high significance. The aim of the present study was to assess the anticancer activity of 4′-hydroxy-3,4,5-trimetoxystilbene (DMU-281), the metabolite of DMU-212, in DLD-1 and LOVO cell lines. We showed for the first time the cytotoxic activity of DMU-281 triggered via cell cycle arrest at G2/M phase and apoptosis induction accompanied by the activation of caspases-9, -8, -3/7. Furthermore, DMU-281 has been found to change the expression pattern of genes and proteins related to intrinsic as well as extrinsic apoptosis. Since the activation of these pathways of apoptosis is still the most desired strategy in anticancer research, DMU-281 seems to provide a promising approach to the treatment of colon cancer.

scholarly journals Isolation and Cytotoxic Activity of Phyllocladanes from the Roots of Acacia schaffneri (Leguminosae)

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3944
Author(s):  
José de Jesús Manríquez-Torres ◽  
Marco Antonio Hernández-Lepe ◽  
José Román Chávez-Méndez ◽  
Susana González-Reyes ◽  
Idanya Rubí Serafín-Higuera ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Spectroscopic Properties ◽  
Cancer Cell Lines ◽  
Moderate Activity ◽  
Cycle Arrest ◽  
Ic50 Values

In research on natural molecules with cytotoxic activity that can be used for the development of new anticancer agents, the cytotoxic activity of hexane, chloroform, and methanol extracts from the roots of Acacia schaffneri against colon, lung, and skin cancer cell lines was explored. The hexane extract showed the best activity with an average IC50 of 10.6 µg mL−1. From this extract, three diterpenoids, phyllocladan-16α,19-diol (1), phyllocladan-16α-ol (2), and phylloclad-16-en-3-ol (3), were isolated and characterized by their physical and spectroscopic properties. Diterpenoids 1 and 2 were tested against the same cancer cell lines, as well as their healthy counterparts, CCD841 CoN, MRC5, and VH10, respectively. Compound 1 showed moderate activity (IC50 values between 24 and 70 μg mL−1), although it showed a selective effect against cancer cell lines. Compound 2 was practically inactive. The cytotoxicity mechanism of 1 was analyzed by cell cycle, indicating that the compound induces G0/G1 cell cycle arrest. This effect might be generated by DNA alkylation damage. In addition, compound 1 decreased migration of HT29 cells.

scholarly journals Radiosensitization Effect of Nedaplatin on Nasopharyngeal Carcinoma Cells in Different Status of Epstein-Barr Virus Infection

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Li Yin ◽  
Jing Wu ◽  
Jianfeng Wu ◽  
Jinjun Ye ◽  
Xuesong Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nasopharyngeal Carcinoma ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Cycle Arrest ◽  
M Phase ◽  
Epstein Barr ◽  
Mts Assay

This study aims to evaluate the radiosensitization effect of nedaplatin on nasopharyngeal carcinoma (NPC) cell lines with different Epstein-Barr virus (EBV) status. Human NPC cell lines CNE-2 (EBV-negative) and C666 (EBV-positive) were treated with 0–100 μg/mL nedaplatin, and inhibitory effects on cell viability and IC50were calculated by MTS assay. We assessed changes in radiosensitivity of cells by MTS and colony formation assays, and detected the apoptosis index and changes in cell cycle by flow cytometry. MTS assay showed that nedaplatin caused significant cytotoxicity in CNE-2 and C666 cells in a time- and dose-dependent manner. After 24 h, nedaplatin inhibited growth of CNE-2 and C666 cells with IC50values of 34.32 and 63.69 μg/mL, respectively. Compared with radiation alone, nedaplatin enhanced the radiation effect on both cell lines. Nedaplatin markedly increased apoptosis and cell cycle arrest in G2/M phase. Nedaplatin radiosensitized human NPC cells CNE-2 and C666, with a significantly greater effect on the former. The mechanisms of radiosensitization include induction of apoptosis and enhancement of cell cycle arrest in G2/M phase.

scholarly journals β-Lapachone Inhibits Lung Metastasis of Colorectal Cancer by Inducing Apoptosis of CT26 Cells

2016 ◽  
Vol 16 (4) ◽  
pp. 585-596 ◽  
Author(s):  
Ji-Ye Kee ◽  
Yo-Han Han ◽  
Jinbong Park ◽  
Dae-Seung Kim ◽  
Jeong-Geon Mun ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Lung Metastasis ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Experimental Metastasis ◽  
Colon Cancer Cell Lines ◽  
Metastasis Model

Background: β-Lapachone is a quinone-containing compound found in red lapacho ( Tabebuia impetiginosa, syn. T avellanedae) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of β-lapachone and the underlying mechanisms using colon cancer cells. Methods: This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38). A WST assay, annexin V assay, cell cycle analysis, wound healing assay, invasion assay, western blot analysis, and real-time reverse transcription–polymerase chain reaction were performed to examine the effects of β-lapachone on metastatic phenotypes and molecular mechanisms. The effect of β-lapachone on lung metastasis was assessed in a mouse experimental metastasis model. Results: We found that the inhibition of proliferation of the colon cancer cell lines by β-lapachone was due to the induction of apoptosis and cell cycle arrest. β-Lapachone induced the apoptosis of CT26 cells through caspase-3, -8, and -9 activation; poly(ADP-ribose) polymerase cleavage; and downregulation of the Bcl-2 family in a dose- and time-dependent manner. In addition, a low concentration of β-lapachone decreased the cell migration and invasion by decreasing the expression of matrix metalloproteinases-2 and -9, and increased the expression of tissue inhibitors of metalloproteinases-1 and -2. Moreover, β-lapachone treatment regulated the expression of epithelial-mesenchymal transition markers such as E- and N-cadherin, vimentin, β-catenin, and Snail in CT26 cells. In the mouse experimental metastasis model, β-lapachone significantly inhibited the lung metastasis of CT26 cells. Conclusions: Our results demonstrated the inhibitory effect of β-lapachone on colorectal lung metastasis. This compound may be useful for developing therapeutic agents to treat metastatic cancer.

Terpyridine Copper(II) Complexes as Potential Anticancer Agents by Inhibiting Cell Proliferation, Blocking Cell Cycle and Inducing Apoptosis in BEL-7402 Cells

2022 ◽  
Author(s):  
Yunqiong Gu ◽  
Yu-Jun Zhong ◽  
Mei-Qi Hu ◽  
Huan-Qing Li ◽  
Kun Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines

Four mononuclear terpyridine complexes [Cu(H-La)Cl2]·CH3OH (1), [Cu(H-La)Cl]ClO4 (2), [Cu(H-Lb)Cl2]·CH3OH (3), and [Cu(H-Lb)(CH3OH)(DMSO)](ClO4)2 (4) were prepared and fully characterized. Complexes 14 exhibited higher cytotoxic activity against several tested cancer cell lines...

Aptamer TY04 Inhibits Multiple Myeloma Cell Growth Via Cell Cycle Arrest

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5390-5390
Author(s):  
Jing Liu ◽  
Hong-Juan Dai ◽  
Bian-Ying Ma ◽  
Jian-Hui Song ◽  
Hui-yong Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Cell Growth ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Multiple Myeloma Cell ◽  
Cycle Arrest ◽  
M Phase ◽  
Target Molecules

Abstract Multiple myeloma (MM), also known as plasma cell myeloma, is characterized by accumulation of clonal plasma cells in the bone marrow and overproduction of monoclonal immunoglobulin (Ig) in the blood or urine. MM accounts for approximately 10% of all hematologic malignancies. Despite recent advances in the understanding and treatment of this disease, MM remains an incurable disease in the vast majority. With conventional chemotherapy, the 5-year median survival rate for MM patients is approximately 25%. Aptamers are single-stranded RNA or DNA sequences that bind to target molecules with high affinity and specificity. Compared with antibodies, aptamers have unique advantages including easy chemical synthesis and modification, low toxicity, lack of immunogenicity, and rapid tissue penetration, Based on these advantages, aptamers show great potential for therapeutic application. The aptamer TY04 is a single-stranded DNA (ssDNA) generated by a method named cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX), We found TY04 strongly inhibited the growth of multiple myeloma cell lines including MM1.S, NCI-H929, KM3 and OPM2,The concentration of TY04 to inhibit 50% cell growth (IC50) on MM1.S was 3.89 μM. In contrast, TY04 had no effect on the growth of non-tumor cell lines — immortal B lymphoblastoid cell lines. Next, we used MM1.S cell line as the model to study the mechanism of TY04 anti- multiple myeloma. Flow cytometry analysis showed that TY04 with the sequence specifically bind to MM1.S cells when compared with unselected ssDNA library control. To investigate whether the target molecules of TY04 are membrane proteins on cell surface, MM1.S cells were treated with trypsin and proteinase k for 2 or 10 minutes before incubation with TY04. The result revealed that TY04 lost partly recognition ability on treated cells, indicating that the target molecules were most likely membrane proteins. Furthermore, we evaluated the cell cycle distribution of MM1.S after TY04 treatment. We found that TY04 significantly caused cell-cycle arrest in G2/M phase. The percentage of G2/M phase cells increased from 30.1±1.56 to 53.2±6.36. To identify the underlying molecular mechanism, G2/M-related proteins were assayed by flow cytometry. Following TY04 treatment, a concomitant inhibition of ERK1/2, cyclin B, CDK1 and γ-tubulin expression occurred. Meanwhile, human cell cycle PCR array was used to analyze the expression of 84 genes key to cell cycle regulation in TY04-treated MM1.S cells. Our results indicated that aptamer TY04 decreased the genes expression of CCNB1, CCNB2, BIRC5, BRCA1 and CCNH, which were involved in the progress of G2/M phase. All these results are significant in that they provide a framework for further exploring the use of TY04 as a novel anti-multiple myeloma agent. Disclosures: No relevant conflicts of interest to declare.

scholarly journals MicroRNA silencing of CNN1 and CNN2 protein family members regulates biology processes in colorectal cancer by targeting the p53 signal pathway

2020 ◽  
Author(s):  
Fuda Huang ◽  
Mingwei Wei ◽  
Anmin Wang ◽  
Ya Zhang ◽  
Zebang Qin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Expression Levels ◽  
Colon Cancer Cell Lines ◽  
Cancer Tissues

Abstract BackgroundCalponin was first defined as a striated muscle troponin T-like protein that binds actin thin filaments to regulate smooth muscle contraction. There are few studies of CNN1 and CNN2 in colorectal cancer, and the roles these two genes play in colorectal cancer cell lines and the mechanisms by which they act are unknown.MethodsWe used immunohistochemistry to identify expression of the two genes in the cancer tissues. RT-PCR was used to measure expression levels of microRNA. W performed western blots to measure changes in signaling pathways in the context of expression interference.Meanwhile, the same method was used to measure binding relationship between the two genes and key pathway proteins. To determine the relationship between microRNA and gene mRNA, we used the reporter gene method. We used the chi-square and t-test methods to analyze the significance and correlations of the data.Results and conclusionsExpression levels of CNN1 were lower in colon cancer tissues than in normal mucosal tissues. After downregulating CNN1, the cell cycle in colon cancer cell lines progressed quickly, and the expression of related pathway proteins also increased. Expression levels of CNN2 were higher in colon cancer tissues, and its downregulation significantly inhibited cell cycle progression in colon cancer cell lines. We confirmed correlations between the expression of microRNA and CNN2 using data analysis.Bars indicate ± standard errors.*p < 0.05; **p < 0.01 compared with the control. The inhibition of the expression of CNN2 mRNA using microRNA was confirmed using western blot. The combination of the two at the mechanism level was also demonstrated using the reporter gene method.

scholarly journals Identification and Validation of Novel Microtubule Suppressors with an Imidazopyridine Scaffold through Structure Based Virtual Screening and Docking.

2021 ◽  
Author(s):  
Samia A Elseginy ◽  
A Sofia F Oliveira ◽  
Deborah K Shoemark ◽  
Richard B Sessions
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Anticancer Agents ◽  
3D Structure ◽  
Cancer Cell Proliferation ◽  
Cycle Arrest ◽  
Colchicine Binding Site ◽  
Apoptotic Protein ◽  
M Phase ◽  
Low Toxicity

Targeting the colchicine binding site of alpha/beta tubulin microtubules can lead to suppression of microtubule dynamics, cell cycle arrest and apoptosis. Therefore, development of microtubule (MT) inhibitors is considered a promising route to anticancer agents. Our approach to identify novel scaffolds as MT inhibitors depends on a 3D-structure based pharmacophore approach and docking using three programmes MOE, Autodock and BUDE (Bristol University Docking Engine) to screen a library of virtual compounds. From this work we identified the compound 7-(3-Hydroxy-4-methoxy-phenyl)-3-(3-trifluoromethyl-phenyl)-6,7-dihydro-3H-imidazo[4,5-b] pyridin-5-ol (6) as a novel inhibitor scaffold. This compound inhibited several types of cancer cell proliferation at low micromolar concentrations with low toxicity. Compound 6 caused cell cycle arrest in the G2/M phase and blocked tubulin polymerization at low micromolar concentration (IC50 = 6 micromolar, inducing apoptosis via activation of caspase 9, increasing the level of the pro-apoptotic protein Bax and decreasing the level of the anti-apoptotic protein Bcl2. In summary, our approach identified a lead compound with potential antimitotic and antiproliferative activity.

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